Correlation between α1-Antitrypsin Deficiency and SARS-CoV-2 Infection: Epidemiological Data and Pathogenetic Hypotheses

The most common hereditary disorder in adults, α1-antitrypsin deficiency (AATD), is characterized by reduced plasma levels or the abnormal functioning of α1-antitrypsin (AAT), a major human blood serine protease inhibitor, which is encoded by the SERine Protein INhibitor-A1 (SERPINA1) gene and produced in the liver. Recently, it has been hypothesized that the geographic differences in COVID-19 infection and fatality rates may be partially explained by ethnic differences in SERPINA1 allele frequencies. In our review, we examined epidemiological data on the correlation between the distribution of AATD, SARS-CoV-2 infection, and COVID-19 mortality rates. Moreover, we described shared pathogenetic pathways that may provide a theoretical basis for our epidemiological findings. We also considered the potential use of AAT augmentation therapy in patients with COVID-19.

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ANALYTICAL EPIDEMIOLOGY OF GASTRIC CANCER IN THE REPUBLIC OF CRIMEA AND ITS CONFORMITY WITH ALL-RUSSIAN TRENDS

Problems in oncology ◽

10.37469/0507-3758-2018-64-5-592-601 ◽

2018 ◽

Vol 64 (5) ◽

pp. 592-601

Author(s):

Viktor Oleksenko ◽

Kazim Aliev ◽

I. Akinshevich ◽

Ye. Chirva

Keyword(s):

Gastric Cancer ◽

Epidemiological Data ◽

Mortality Rates ◽

Similar Data ◽

Results Of Treatment ◽

Mortality Index ◽

World Standard ◽

The Russian Federation ◽

The Republic ◽

National Trends

Gastric cancer (GC) is one of the most common malignant tumor, both world-wide and in the Russian Federation (RF), possessing one of the highest mortality rates. The aim of current research was to analyze the main epidemiological data, the rates reflecting the diagnostics and results of treatment of GC patients in the Republic of Crimea (RC) and to compare with national trends. Using the extensive, intensive, standardized rates, estimated by world standard method, structural analysis of the epidemiology of GC in RC for the period from 2007 to 2016 was carried out. The obtained results made it possible to compare these data with the main GC rates in RF. Results of the study. The incidence of GC in RC decreased during 10 years, for men - 16,42 (4th place), for women - 6,68 (9th place) per 100 000 of the population. By 2021 a further decline in morbidity in men is expected to be 30,27% and a possible increase in the female incidence rate - by 17,54%. The average age of GC patients in RC was 66,5 years. Index accuracy was 0,75, which testified to satisfactory conditions of specialized treatment for this tumor. Mortality from GC at the 1st year of life in RC was higher than in RF - 56,0%, which was due to low active diagnostics - 3,6% and accordingly a high proportion of GC patients of IV stage - 43,3%. Ratio index in RC for 10 years was higher than in RF and increased from 3,5 to 4,4; prevalence rate of GC in RC was lower - 84,1 per 100 000 of the population in comparison with RF, GC mortality index - 15,3 per 100 000 of the population that was lower than in RF. The proportion of patients who have been observed for 5 years or more in RC was 57,3% that was more than in RF. Conclusions. The rates reflecting early diagnostics of GC in RC are worse than all-Russian ones, which makes it necessary to develop medical examination program for the population of RC for this malignancy. The growth of ratio index, the lower mortality rates and the greater proportion of people who have been observed for 5 years or more indicates the best results of treatment of patients with GC in RC compared with similar data in RF.

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The Joy of Statistics

10.1093/oso/9780198833444.001.0001 ◽

2019 ◽

Cited By ~ 1

Author(s):

Steve Selvin

Keyword(s):

Coronary Heart Disease ◽

Short Stories ◽

Heart Disease ◽

Infant Mortality ◽

Statistical Methods ◽

Ethnic Differences ◽

Coronary Heart Disease Risk ◽

Disease Risk ◽

Mortality Rates ◽

Heart Disease Risk

The Joy of Statistics consists of a series of 42 “short stories,” each illustrating how elementary statistical methods are applied to data to produce insight and solutions to the questions data are collected to answer. The text contains brief histories of the evolution of statistical methods and a number of brief biographies of the most famous statisticians of the 20th century. Also throughout are a few statistical jokes, puzzles, and traditional stories. The level of the Joy of Statistics is elementary and explores a variety of statistical applications using graphs and plots, along with detailed and intuitive descriptions and occasionally using a bit of 10th grade mathematics. Examples of a few of the topics are gambling games such as roulette, blackjack, and lotteries as well as more serious subjects such as comparison of black/white infant mortality rates, coronary heart disease risk, and ethnic differences in Hodgkin’s disease. The statistical description of these methods and topics are accompanied by easy to understand explanations labeled “how it works.”

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The Potential Use of Vitamin C to Prevent Kidney Injury in Patients with COVID-19

Diseases ◽

10.3390/diseases9030046 ◽

2021 ◽

Vol 9 (3) ◽

pp. 46

Author(s):

Feng Xu ◽

Yawei Wen ◽

Xinge Hu ◽

Tiannan Wang ◽

Guoxun Chen

Keyword(s):

Vitamin C ◽

Distress Syndrome ◽

Kidney Injury ◽

Mortality Rates ◽

Protective Effects ◽

Global Public Health ◽

Health Crisis ◽

Public Health Crisis ◽

Renal Functions ◽

Potential Use

The newly found SARS-CoV-2 has led to the pandemic of COVID-19, which has caused respiratory distress syndrome and even death worldwide. This has become a global public health crisis. Unfortunately, elders and subjects with comorbidities have high mortality rates. One main feature of COVID-19 is the cytokine storm, which can cause damage in cells and tissues including the kidneys. Here, we reviewed the current literature on renal impairments in patients with COVID-19 and analyzed the possible etiology and mechanisms. In addition, we investigated the potential use of vitamin C for the prevention of renal injury in those patients. It appears that vitamin C could be helpful to improve the outcomes of patients with COVID-19. Lastly, we discussed the possible protective effects of vitamin C on renal functions in COVID-19 patients with existing kidney conditions.

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Management of lung disease in alpha-1 antitrypsin deficiency: what we do and what we do not know

Therapeutic Advances in Chronic Disease ◽

10.1177/20406223211010172 ◽

2021 ◽

Vol 12_suppl ◽

pp. 204062232110101

Author(s):

Igor Barjaktarevic ◽

Michael Campos

Keyword(s):

Lung Disease ◽

Treatment Guidelines ◽

Management Program ◽

Lifestyle Changes ◽

Chronic Obstructive ◽

Augmentation Therapy ◽

Lung Function Decline ◽

Antitrypsin Deficiency ◽

Alpha 1 Antitrypsin Deficiency ◽

Alpha 1 Antitrypsin

Management of lung disease in patients with alpha-1 antitrypsin deficiency (AATD) includes both non-pharmacological and pharmacological approaches. Lifestyle changes with avoidance of environmental pollutants, including tobacco smoke, improving exercise levels and nutritional status, all encompassed under a disease management program, are crucial pillars of AATD management. Non-pharmacological therapies follow conventional treatment guidelines for chronic obstructive pulmonary disease. Specific pharmacological treatment consists of administering exogenous alpha-1 antitrypsin (AAT) protein intravenously (augmentation therapy). This intervention raises AAT levels in serum and lung epithelial lining fluid, increases anti-elastase capacity, and decreases several inflammatory mediators in the lung. Radiologically, augmentation therapy reduces lung density loss over time, thus delaying disease progression. The effect of augmentation therapy on other lung-related outcomes, such as exacerbation frequency/length, quality of life, lung function decline, and mortality, are less clear and questions regarding dose optimization or route of administration are still debatable. This review discusses the rationale and available evidence for these interventions in AATD.

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Protease-Specific Biomarkers to Analyse Protease Inhibitors for Emphysema Associated with Alpha 1-Antitrypsin Deficiency. An Overview of Current Approaches

International Journal of Molecular Sciences ◽

10.3390/ijms22031065 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1065

Author(s):

Simona Viglio ◽

Elisabeth G. Bak ◽

Iris G. M. Schouten ◽

Paolo Iadarola ◽

Jan Stolk

Keyword(s):

Serine Proteases ◽

Lung Parenchyma ◽

New Drugs ◽

Chronic Obstructive ◽

Augmentation Therapy ◽

Lung Function Decline ◽

Obstructive Pulmonary Disease ◽

Antitrypsin Deficiency ◽

Novel Biomarkers ◽

Alpha1 Antitrypsin

As a known genetic cause of chronic obstructive pulmonary disease (COPD), alpha1-antitrypsin deficiency (AATD) can cause severe respiratory problems at a relatively young age. These problems are caused by decreased or absent levels of alpha1-antitrypsin (AAT), an antiprotease which is primarily functional in the respiratory system. If the levels of AAT fall below the protective threshold of 11 µM, the neutrophil-derived serine proteases neutrophil elastase (NE) and proteinase 3 (PR3), which are targets of AAT, are not sufficiently inhibited, resulting in excessive degradation of the lung parenchyma, increased inflammation, and increased susceptibility to infections. Because other therapies are still in the early phases of development, the only therapy currently available for AATD is AAT augmentation therapy. The controversy surrounding AAT augmentation therapy concerns its efficiency, as protection of lung function decline is not demonstrated, despite the treatment’s proven significant effect on lung density change in the long term. In this review article, novel biomarkers of NE and PR3 activity and their use to assess the efficacy of AAT augmentation therapy are discussed. Furthermore, a series of seven synthetic NE and PR3 inhibitors that can be used to evaluate the specificity of the novel biomarkers, and with potential as new drugs, are discussed.

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Augmentation Therapy for ??1-Antitrypsin Deficiency

Drugs ◽

10.2165/00003495-200464160-00002 ◽

2004 ◽

Vol 64 (16) ◽

pp. 1743-1756 ◽

Cited By ~ 10

Author(s):

Georges S Juvelekian ◽

James K Stoller

Keyword(s):

Augmentation Therapy ◽

Antitrypsin Deficiency

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Uterine cancer at a glance

JOURNAL of SIBERIAN MEDICAL SCIENCES ◽

10.31549/2542-1174-2021-3-116-136 ◽

2021 ◽

pp. 116-136

Author(s):

N. Mimoune ◽

◽

M.Y. Azzouz ◽

O. Benadjel ◽

D. Khelef ◽

...

Keyword(s):

Lower Limb ◽

Sampling Method ◽

Uterine Cancer ◽

Gynecological Cancer ◽

Epidemiological Data ◽

Mortality Rates ◽

Gynecological Tumors ◽

Approximate Estimate ◽

Common Cancer ◽

Simple Average

Among gynecological tumors, malignant uterine tumor (MUT) is the 6th most common cancer in women and the 15th most common cancer overall. There were approximately 382 069 new cases and 89 929 deaths attributed to this type worldwide in 2018. Therefore, MUT was the second most common gynecological cancer and the fourth leading cause of death due to gynecological cancer in 2018, and is expected to increase the incidence rate by more than 50% globally by 2040. Mortality rates are lowest in Central and South Asia and most of Africa. Survivors of MUT may experience treatment-related issues, including infertility, early onset of menopause, sexual problems, and lower limb lymphedema. Wbuilds its own database from national modeling incidence estimates, using incidence ratios with a sampling method that relies on the calculation of a weighted or simple average of the most popular local rates applied to the population of a few regions or by an approximate estimate based on data provided by health establishments in neighboring countries. While in Algeria, existing statistical and epidemiological data and updated information on the pathology are insuffi cient. The objective of this work is to highlight the importance and the situation of the MUT in this country and to describe the different recent aspects (etiology, diagnostics and treatment) related to the disease.

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